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Volume 10 ， Issue 6 ， 2023
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Abstract：Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective, and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts’ clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts’ consensus.Keywords：Continuous renal replacement therapy;Emergency;anticoagulation;Citrate;Guideline;Expert consensus67|0|0Updated：2024-01-23
POSITION ARTICLE AND GUIDELINE
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Explosive eye injuries: characteristics, traumatic mechanisms, and prognostic factors for poor visual outcomes AI Introduction
Abstract：Background:Explosions can produce blast waves, high-speed medium, thermal radiation, and chemical spatter, leading to complex and compound eye injuries. However, few studies have comprehensively investigated the clinical features of different eye injury types or possible risk factors for poor prognosis.Methods:We retrospectively reviewed all consecutive records of explosive eye injuries (1449 eyes in 1115 inpatients) in 14 tertiary referral hospitals in China over 12 years (between January 1, 2008 and December 31, 2019). Data on demographics, eye injury types, ocular findings, treatments, and factors affecting visual prognosis were extracted from a standardized database of eye injuries and statistically analyzed.Results:Mechanical ocular trauma accounted for 94.00% of explosion-related eye injuries, among which intraocular foreign bodies (IOFBs) resulted in 55.17% of open globe injuries (OGIs) and contusion caused 60.22% of close globe injuries (CGIs). Proliferative vitreous retinopathy (PVR) was more common in perforating (47.06%) and IOFB (26.84%) than in penetrating (8.79%) injuries, and more common with laceration (24.25%) than rupture (9.22%, P<0.01). However, no difference was observed between rupture and contusion. Ultimately, 9.59% of eyes were removed and the final vision was ≤4/200 in 45.82% of patients. Poor presenting vision [odds ratio (OR)=5.789], full-thickness laceration of the eyeball ≥5 mm (OR=3.665), vitreous hemorrhage (OR=3.474), IOFB (OR=3.510), non-mechanical eye injury (NMEI, OR=2.622), rupture (OR=2.362), traumatic optic neuropathy (OR=2.102), retinal detachment (RD, OR=2.033), endophthalmitis (OR=3.281), contusion (OR=1.679), ciliary body detachment (OR=6.592), zone Ⅲ OGI (OR=1.940), and PVR (OR=1.615) were significant negative predictors for poor visual outcomes (P<0.05).Conclusions:Explosion ocular trauma has complex mechanisms, with multiple eyes involved and poor prognosis. In lethal level Ⅰ explosion injuries, eyeball rupture is a serious condition, whereas contusion is more likely to improve. In level Ⅱ injuries, IOFBs are more harmful than penetrating injuries, and level Ⅳ represents burn-related eye injuries. PVR is more associated with penetrating mechanisms than with OGI. Identifying the risk predictors for visual prognosis can guide clinicians in the evaluation and treatment of ocular blast injuries.Keywords：Explosion-related eye injury;Mechanical ocular trauma;Visual outcome;Risk factor36|0|0Updated：2024-01-23 -
Abstract：BackgroundReconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging.MethodsThis study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery.ResultsACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9±50.1) J/m2 for the heart, (607.6±30.0) J/m2 for the intestine, (473.7±37.0) J/m2 for the liver, (186.1±13.3) J/m2 for the muscle, and (579.3±32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8±1.2)% for LO2 and (98.3±1.6)% for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P=0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P=0.40 compared with suture anastomosis). Additionally, ACP-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface.ConclusionsACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.Keywords：Tissue reconstruction;Wet adhesion;Adhesive hydrogel;Bioadhesive42|0|0Updated：2024-01-23 -
Single-cell transcriptome profiling of sepsis identifies
HLA-DRlow S100Ahigh monocytes with immunosuppressive function AI Introduction
Abstract：BackgroundSustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.MethodsWe adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9–/– mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.ResultsscRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.ConclusionsThis study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.Keywords：Single-cell analysis;sepsis;immunosuppression;S100A;Human leukocyte antigen DR (HLA-DR);Monocytes;Myeloid-derived suppressor cells (MDSCs);Paquinimod34|0|0Updated：2024-01-23
RESEARCH
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Abstract：Fungi and bacteria afflict humans with innumerous pathogen-related infections and ailments. Most of the commonly employed microbicidal agents target commensal and pathogenic microorganisms without discrimination. To distinguish and fight the pathogenic species out of the microflora, novel antimicrobials have been developed that selectively target specific bacteria and fungi. The cell wall features and antimicrobial mechanisms that these microorganisms involved in are highlighted in the present review. This is followed by reviewing the design of antimicrobials that selectively combat a specific community of microbes including Gram-positive and Gram-negative bacterial strains as well as fungi. Finally, recent advances in the antimicrobial immunomodulation strategy that enables treating microorganism infections with high specificity are reviewed. These basic tenets will enable the avid reader to design novel approaches and compounds for antibacterial and antifungal applications.Keywords：Antimicrobial nanotechnology;Immumodualtion;Selective toxicity;Smart nanomaterials;Targeting microorganism25|0|0Updated：2024-01-23 -
Abstract：Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA (pDNA) and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.Keywords：Ionizable nanomaterials;Ionizable drug delivery systems (IDDSs);Nucleic acids;gene therapy21|1|0Updated：2023-04-26 -
Applications and prospects of cryo-EM in drug discovery AI Introduction
Abstract：Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.Keywords：Cryo-electron microscopy (cryo-EM);Drug discovery;Structure-based drug design;Fragment-based drug discovery;Proteolysis targeting chimeras;Drug repurposing;Artificial intelligence (AI)21|0|0Updated：2023-04-26 -
Recent advances in CRISPR-based genome editing technology and its applications in cardiovascular research AI Introduction
Abstract：The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing toolbox has been greatly expanded, not only with emerging CRISPR-associated protein (Cas) nucleases, but also novel applications through combination with diverse effectors. Recently, transposon-associated programmable RNA-guided genome editing systems have been uncovered, adding myriads of potential new tools to the genome editing toolbox. CRISPR-based genome editing technology has also revolutionized cardiovascular research. Here we first summarize the advances involving newly identified Cas orthologs, engineered variants and novel genome editing systems, and then discuss the applications of the CRISPR-Cas systems in precise genome editing, such as base editing and prime editing. We also highlight recent progress in cardiovascular research using CRISPR-based genome editing technologies, including the generation of genetically modified in vitro and animal models of cardiovascular diseases (CVD) as well as the applications in treating different types of CVD. Finally, the current limitations and future prospects of genome editing technologies are discussed.Keywords：Genome editing;CRISPR-Cas system;Base editing;Prime editing;Transposon-associated genome editing;Cardiovascular disease;heart;Blood vessel;gene therapy34|1|0Updated：2024-01-23
REVIEW
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Advancing our understanding of monocyte HLA-DR, S100A9, and the potential for individualized therapies in sepsis AI Introduction
Keywords：sepsis;Monocyte;HLA-DR;S100A9;immunosuppression15|0|0Updated：2024-01-23
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